Talquetamab improves patient reported symptoms and health related quality of life in relapsed or refractory multiple myeloma Results from the phase 12 MonumenTAL1 study summary

In this PACUPod episode, we examine the MonumenTAL-1 Phase 2 study of talquetamab in relapsed or refractory multiple myeloma (RRMM). Using patient-reported outcomes collected with EORTC QLQ-C30, EQ-5D-5L, and PGIS, the study shows transient symptom worsening in cycle 1 followed by clinically meaningful improvements through cycle 21, including enhancements in global health status and emotional functioning, with notable reductions in pain and fatigue. We discuss the patient population (triple-class exposed RRMM with high-risk cytogenetics and extramedullary disease), dosing (0.8 mg/kg every other week), and the single-arm design, along with safety considerations (early but manageable cytokine release syndrome and skin/oral toxicities). Limitations such as open-label design and small sample size are considered, as are clinical implications for integrating PROs into routine care and real-world practice. The episode highlights how improved patient-reported outcomes can complement disease control in a challenging patient group.

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Britany: Welcome back to PACULit, your daily clinical literature update. Today, we’re discussing the Phase 2 MonumenTAL-1 study evaluating talquetamab in relapsed or refractory multiple myeloma (RRMM). Seth, great to have you here to unpack the latest data on patient-reported outcomes (PROs) and quality of life.

Seth: Thanks, Britany. RRMM, especially in triple-class exposed patients—those treated with proteasome inhibitors, immunomodulatory drugs, and anti-CD38 antibodies—remains challenging. New therapies that control disease and improve quality of life are crucial.

Britany: Exactly. Despite advances, MM is incurable, and heavily pretreated patients suffer significant symptom burden and impaired health-related quality of life (HRQoL). The MonumenTAL-1 study’s focus on PROs fills a gap beyond traditional efficacy endpoints.

Seth: Talquetamab is a bispecific antibody targeting GPRC5D on myeloma cells and CD3 on T-cells, redirecting immune cells to attack tumors. Prior studies showed promising response rates, but data on patient experience during treatment were limited until now.

Britany: As survival improves, more patients become refractory, increasing unmet needs. Managing symptoms and maintaining quality of life alongside disease control is vital.

Seth: The study included patients with high-risk cytogenetics and extramedullary disease—populations often excluded from trials—enhancing real-world applicability.

Britany: MonumenTAL-1 was a Phase 2, open-label, single-arm trial. PRO analysis was a secondary endpoint but well integrated. Patients were adults with RRMM, triple-class exposed, with at least three prior therapy lines, adequate organ function, and performance status.

Seth: Patients with active infections, uncontrolled comorbidities, or prior talquetamab exposure were excluded to ensure safety and clearer drug effect interpretation.

Britany: Talquetamab was given at 0.8 mg/kg subcutaneously every other week, based on prior data showing effective T-cell activation and therapeutic exposure.

Seth: Without a comparator arm, the study focused on longitudinal PRO assessment using validated tools: EORTC QLQ-C30 (global health, function, symptoms), EQ-5D-5L Visual Analog Scale (overall health), and Patient Global Impression of Severity (PGIS).

Britany: PROs were collected at baseline and multiple visits up to cycle 21 (~42 weeks), allowing tracking of short- and long-term changes.

Seth: Descriptive statistics were used for PRO comparisons, appropriate for a single-arm design. Compliance was high—over 95% at baseline and above 80% at most visits—supporting data reliability.

Britany: Key findings showed transient PRO worsening during cycle 1, likely from early adverse effects. Afterward, significant improvements emerged. By cycle 21, global health status improved by 4.9 points, emotional functioning by 12.5 points—clinically meaningful changes.

Seth: Pain and fatigue, major RRMM symptoms, decreased notably—pain by 11.4 points, fatigue by 4.0 points—substantially impacting daily life.

Britany: More patients experienced clinically meaningful improvements or maintained baseline status over time. EQ-5D-5L VAS and PGIS scores also trended toward better quality of life.

Seth: Despite initial side effects, patients generally felt better as treatment continued. This matches talquetamab’s safety profile, where early cytokine release syndrome and skin or oral toxicities are manageable and transient.

Britany: Rasche et al. (2023) highlighted cytokine release syndrome incidence with talquetamab, emphasizing monitoring and management, further detailed by Touzeau et al. (2024).

Seth: These strategies are critical for clinicians to keep patients on therapy and maximize benefit. Early education and proactive symptom management can mitigate initial PRO worsening.

Britany: Gong et al. (2025) showed the 0.8 mg/kg every-other-week dose balances efficacy and tolerability via effective pharmacologic exposure and T-cell activation.

Seth: Optimizing dose and schedule is essential, especially in heavily pretreated patients with compromised organ function or performance status.

Britany: Tomlinson et al. (2024) reported positive outcomes in high-risk cytogenetics and extramedullary disease patients treated with talquetamab, supporting its use in difficult subpopulations.

Seth: The broad applicability is encouraging. Limitations include the open-label design, which may introduce expectation bias, and a relatively small sample size (118 patients) for long-term PRO data.

Britany: Also, without a comparator arm, direct PRO comparisons to other therapies aren’t possible. Still, consistent improvements across validated instruments strengthen the findings.

Seth: Clinically, talquetamab offers a promising option for triple-class exposed RRMM patients, improving disease control and quality of life.

Britany: Pharmacists should monitor early adverse events, educate patients on expectations, and support symptom management to maintain adherence and maximize benefit.

Seth: Considering drug interactions is important. Talquetamab’s bispecific antibody mechanism doesn’t involve cytochrome P450 metabolism, but concomitant immunosuppressants or corticosteroids used for side effects may affect immune function.

Britany: Tailoring supportive care and monitoring immune status is essential, especially in patients with comorbidities or multiple therapies.

Seth: Special populations like elderly or renal-impaired patients were included to some extent, but more real-world data are needed to clarify safety and efficacy.

Britany: Future studies comparing talquetamab directly with other T-cell redirecting therapies or standard care would help contextualize these PRO improvements.

Seth: To sum up, MonumenTAL-1 shows talquetamab achieves meaningful clinical responses and improves patient-reported symptoms and HRQoL over time in heavily pretreated RRMM.

Britany: Absolutely. Integrating patient-centered outcomes into clinical decisions is vital. Talquetamab represents a significant advancement, offering hope for better symptom control and quality of life in a challenging population.

Seth: Thanks for the discussion, Britany. I’m sure listeners will find these insights useful.

Britany: Thank you, Seth, and thanks to our listeners. Check out the full study by Schinke et al. in Cancer 2025 for more details. Until next time, stay curious and keep advancing patient care.

Seth: Before we wrap up, Britany, I think it’s worth emphasizing how these PRO findings can influence clinical practice. Often, we focus heavily on response rates and survival metrics, but understanding how patients feel during treatment is equally important.

Britany: Absolutely, Seth. For patients with RRMM, who have endured multiple lines of therapy, maintaining or improving quality of life can sometimes be as meaningful as extending survival. Talquetamab’s ability to reduce pain and fatigue, as shown in the study, could translate into better daily functioning and independence.

Seth: And that’s where multidisciplinary care teams come in. Incorporating pharmacists, nurses, and supportive care specialists to monitor symptoms and manage side effects proactively can help patients stay on therapy longer and derive maximum benefit.

Britany: Right. Plus, educating patients about the expected course of side effects—like the transient nature of cytokine release syndrome or skin reactions—can alleviate anxiety and improve adherence.

Seth: Another point is the potential for talquetamab to be combined with other agents in the future. Given its unique mechanism targeting GPRC5D, combining it with other immunotherapies or novel agents might further enhance efficacy without overlapping toxicities.

Britany: That’s an exciting avenue. Ongoing trials are exploring such combinations, and hopefully, future PRO data will continue to highlight patient-centered benefits.

Seth: In the meantime, clinicians should remain vigilant for immune-related adverse events and tailor supportive care accordingly, especially since these patients often have complex medical histories.

Britany: Indeed. And as more real-world evidence accumulates, we’ll better understand how talquetamab performs outside clinical trials, including in more diverse patient populations.

Seth: To our listeners, remember that integrating PROs into routine practice not only informs treatment decisions but also empowers patients by validating their experiences.

Britany: Well said, Seth. Thanks again for this insightful discussion. We look forward to sharing more updates as the field evolves.

Seth: Thanks, Britany. And thanks to everyone tuning in. Stay well and keep prioritizing patient-centered care.